Cancers are characterized by unregulated cell growth, tissue invasion, and metastasis. A neoplasm is benign when it grows in an unregulated fashion without tissue invasion. The presence of both features is characteristic of malignant neoplasms. Cancers are named based on their origin: those derived from epithelial tissue are called carcinomas, those derived from mesenchymal tissues are sarcomas, and those derived from hematopoietic tissue are leukemias or lymphomas.
Cancers nearly always arise as a consequence of genetic alterations. Choriocarcinoma may be an exception to this rule in that experimental insertion of a choriocarcinoma cell into an animal blastocyst can result in the neoplastic cell giving rise to normal body structures under the inductive influence of the developing embryo. Such an occurrence would be unlikely in the setting of irreversible genetic damage.
Occasional cancers appear to be caused by an alteration in a dominant gene that drives uncontrolled cell proliferation. Examples include chronic myeloid leukemia (abl) and Burkitt's lymphoma (c-myc). The genes that can promote cell growth when altered are often called oncogenes. They were first identified as critical elements of viruses that cause animal tumors; later it was found that the viral genes had normal counterparts with important functions in the cell and had been captured and mutated by viruses as they passed from host to host.
However, the vast majority of human cancers are characterized by multiple genetic abnormalities, each of which contributes to the loss of control of cell proliferation and differentiation and the acquisition of capabilities, such as tissue invasion and angiogenesis. Many cancers go through recognizable steps of progressively more abnormal phenotypes: hyperplasia to adenoma to dysplasia to carcinoma in situ to invasive cancer (Table 25-1). These properties are not found in the normal adult cell from which the tumor is derived. Indeed, normal cells have a large number of safeguards against uncontrolled proliferation and invasion.
TABLE 25-1PHENOTYPIC CHARACTERISTICS OF MALIGNANT CELLS |Favorite Table|Download (.pdf) TABLE 25-1PHENOTYPIC CHARACTERISTICS OF MALIGNANT CELLS
|Deregulated cell proliferation: Loss of function of negative growth regulators (suppressor oncogenes, i.e., Rb, p53), and increased action of positive growth regulators (oncogenes, i.e., Ras, Myc). Leads to aberrant cell cycle control and includes loss of normal checkpoint responses. |
|Failure to differentiate: Arrest at a stage before terminal differentiation. May retain stem cell properties. (Frequently observed in leukemias due to transcriptional repression of developmental programs by the gene products of chromosomal translocations.) |
|Loss of normal apoptosis pathways: Inactivation of p53, increases in Bcl-2 family members. This defect enhances the survival of cells with oncogenic mutations and genetic instability and allows clonal expansion and diversification within the tumor without activation of physiologic cell death pathways. |
|Genetic instability: Defects in DNA repair pathways leading to either single or oligo-nucleotide mutations (as in microsatellite instability, MIN) ...|